Cartilage Dysfunction in ALS Patients as Side Effect of Motion Loss: 3D Mechano-Electrochemical Computational Model

Abstract

Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease characterized by progressive weakness, muscle atrophy, and fasciculation. This fact results in a continuous degeneration and dysfunction of articular soft tissues. Specifically, cartilage is an avascular and nonneural connective tissue that allows smooth motion in diarthrodial joints. Due to the avascular nature of cartilage tissue, cells nutrition and by-product exchange are intermittently occurring during joint motions. Reduced mobility results in a change of proteoglycan density, osmotic pressure, and permeability of the tissue. This work aims to demonstrate the abnormal cartilage deformation in progressive immobilized articular cartilage for ALS patients. For this aim a novel 3D mechano-electrochemical model based on the triphasic theory for charged hydrated soft tissues is developed. ALS patient parameters such as tissue porosity, osmotic coefficient, and fixed anions were incorporated. Considering different mobility reduction of each phase of the disease, results predicted the degree of tissue degeneration and the reduction of its capacity for deformation. The present model can be a useful tool to predict the evolution of joints in ALS patients and the necessity of including specific cartilage protectors, drugs, or maintenance physical activities as part of the symptomatic treatment in amyotrophic lateral sclerosis.

Altered swelling and ion fluxes in articular cartilage as a biomarker in osteoarthritis and joint immobilization: a computational analysis

“…These phases dynamically interact with each other triggering essential mechano-electrochemical phenomena for cartilage maintenance (for more details, see [10,38]). Accordingly, the articular cartilage tissue is considered as a mixture of these four phases.…”

“…This technique can provide insights into correlation between intrinsic properties of cartilage and their effects in tissue behaviour which can help in clinical diagnosis and prognosis [28,29]. Despite the high number of existing material models to simulate cartilage behaviour [30][31][32][33], a marked tendency to consider multicomponent and multiphasic models has been established: from purely poromechanic models, where the tissue is considered as a mixture composed of a solid matrix with fluid inside the pores [34,35], to triphasic models, where the role of ions is also incorporated by a new ionic phase [36][37][38]. The interaction between the main tissue components generates specific electrochemical forces, these essential phenomena, which are neglected by most of the previous works, enable analysis of, for instance, the effects of cartilage disease on tissue behaviour.…”

Parameter-dependent behavior of articular cartilage: 3D mechano-electrochemical computational model

“…Based on our previous work (Manzano et al 2014a) four phases are considered: negatively charged porous-elastic solid (s), fluid (f), cations (+) and anions (-). These phases dynamically interact with each other triggering essential mechanoelectrochemical phenomena for cartilage maintenance (for more details see (Sun et al 2004;Manzano et al 2014a;Manzano et al 2014b) …”

“…In the literature many material models for articular cartilage can be found. These models range from relatively simple, including the biphasic nature of the tissue (Higginson et al, 1976;Chen et al 1997), to models that include descriptions of all major individual components of the cartilage (Mow and Guo 2002;Ateshian et al 2013;Manzano et al 2014a;Manzano et al 2014b;Sun et al 2004). However, the main parameters to consider in these simulations remain still obscure since the requirements of a material model are highly dependent on the particular question under research.…”

“…To solve these questions a previous developed three-dimensional mechanoelectrochemical model (Manzano et al 2014a;Manzano et al 2014 b) has been used to analyze and quantify the influence of each parameter variation into cartilage behavior. Specifically, Young´s modulus (E ), Poisson coefficient (ν), cation and anion diffusivities (D + and D -respectively), cation and anion activity coefficient (γ + and γ -respectively) changes have been addressed.…”